Monday, August 15, 2011

AMP v. PTO Does Not Appear to Invalidate Very Many Gene Patent Method Claims

In this post, I explain why my recent analysis of 533 patents identified by Jensen and Murray as "gene patents" (described in a previous post) suggests the Federal Circuit’s recent decision in AMP v. PTO implicates the validity of very few gene patent method claims.

Background

As I pointed out in a blog post last December, the patent eligibility of Myriad's claims to methods of detecting mutations in the BRCA gene by "analyzing" or "comparing" DNA sequences hinged entirely on the court's interpretation of the word "sequence" as it appears in the claims. In the field of molecular biology, the term "sequence" is routinely used not only to refer to the description of the chemical structure of a DNA molecule, but also to the actual DNA molecule as well.

For example, a scientist might say that "I determined the sequence of the BRCA gene." In this context, she is using the word sequence in reference to the abstract description of the order of nucleotides appearing in the gene. But the same scientist might also say that "I cloned the BRCA sequence into an expression vector," in which case she is using the term "sequence" to refer to the DNA molecule itself.

In the first example, "sequence" refers to abstract information describing a chemical structure, while in the second "sequence" is used to refer to a physical object, i.e., a specific DNA molecule. Molecular biologists are usually not bothered by the dual meaning of "sequence," because in practice the meaning of the term is understood based on the context in which it is used. However, it can lead to ambiguity, as seen in AMP v. PTO.

In AMP v. PTO, Myriad argued that as used in its claims the term "sequence" refers to an actual DNA molecule, and thus that analyzing or comparing "sequences of the BRCA gene" would involve physically manipulating and processing molecules in a manner that would render the claims patent eligible under Prometheus. I think it is clear that if the court had adopted this interpretation of "sequence" it would have upheld the validity of the claims. The ACLU plaintiffs never argued that a method claim that requires the analysis of physical DNA molecules would be patent ineligible.

Instead, as explained in a previous post, the ACLU's case was based on its argument that the term "sequence" in the claims refers to information, not to a physical molecule, and hence would cover the mental activity of analyzing or comparing genetic information. The court adopted the ACLU's interpretation of "sequence,” and ruled the claims patent ineligible for claiming nothing more than a mental step. This outcome was specifically dictated by the Federal Circuit’s earlier Prometheus decision, where it stated that a claim directed only to mental analysis of information is patent ineligible.

The Federal Circuit based its interpretation of “sequence” on its finding that Myriad's patent specifications implicitly defined “sequence” broadly to cover pure information, as set forth in this excerpt from the case:

The patent specifications make clear that “sequence” does not exclusively specify a DNA molecule, but refers more broadly to the linear sequence of nucleotide bases of a DNA molecule. For example, Figure 10A–10H is described as showing the “genomic sequence of BRCA1.” ′473 patent col.5 l.66. Figure 10 does not show a physical DNA molecule; the figure lists a series of letters (Gs, As, Ts, and Cs) corresponding to the nucleotides guanine, adenine, thymine, and cytosine of a DNA molecule. Similarly, the patent specifications state that “[t]he nucleotide sequence for BRCA1 exon 4 is shown in SEQ ID NO: 11.” Id. col.53 ll.50–53. SEQ ID NO: 11 again lists a series of Gs, As, Ts, and Cs corresponding to the nucleotide sequence of BRCA1 exon 4.

Thus, Myriad’s claims might very well have been found patent eligible if the specification had defined the term "sequence" to refer only the DNA molecule itself. Alternatively, the claim probably would have been found patent eligible if it recited analyzing "DNA molecules" instead of analyzing sequences. If the claims could only be infringed by someone who physically analyzes the DNA molecule, it would certainly be patent eligible under the Federal Circuit's interpretation of Bilski as set forth in Prometheus.

Claims that could be infringed by merely analyzing genetic data appear to be rare in Jensen and Murray dataset

In essence, Myriad’s method claims were patent ineligible because, as interpreted by the court, they could be infringed by analysis of genetic information. However, my research suggests that few if any of the gene patents identified by Jensen and Murray fall into this category. To the contrary, the vast majority of the claims in these patents would appear to be patent eligible.

Of the 533 patents I analyzed in my study, I only found 12 that included a claim reciting a method of analyzing a DNA sequence for a mutation or variation, and most if not all of those claims appear to require a physical manipulation of a patient's DNA in order for there to be infringement.

In 8 of the 12 patents (6,395,482; 6,087,107; 6,458,541; 6,743,579; 5,830,649; 5,840,486; 5,955,265; and 6,410,226) the broadest claims specifically require obtaining a sample from a patient's body, or analyzing for the genetic variation directly in a patient's body.

For example, Claim 1 of US patent number 6,395,482 recites:

1. A method for determining susceptibility in a human subject to schizophrenia wherein the method comprises the steps of:

(a) removing a bodily sample from the subject, wherein the sample comprises a polynucleotide sequence of a PRODH gene;

(b) determining whether the PRODH gene of the bodily sample comprises a DNA sequence comprising a variation in SEQ ID NO:1 consisting of a T to C transition in the first position of codon 497, such that the presence of said variation in said PRODH gene is indicative of said subject's susceptibility to schizophrenia.

These eight claims would all appear to be patent eligible under AMP and Prometheus because they all involve physically manipulating a human sample obtained from patient.

The remaining four of the 12 patents (5,916,748; 6,630,304; 5,989,815; 6,432,644) are a little more ambiguous, and do not explicitly recite obtaining or analyzing a bodily sample. But arguably all of these claims do require physical manipulation of a sample, depending upon how a court interprets the claim, which will depend in part on how the claim terms were used in the patent specification

For example, Claim 1 of 6,432,644 recites:

1. A method for diagnosing the presence of a polymorphism in human KCNE1 (the coding region of which is bases 193-579 of SEQ ID NO:3) which causes long QT syndrome wherein said method is performed by means which identify the presence of said polymorphism, wherein said polymorphism is one which results in the presence of a KCNE1 polypeptide of SEQ ID NO:4 with an altered amino acid, said altered amino acid being selected from the group consisting of: a) a Leu at residue 74.

Note that this claim uses "means plus function" language, and would probably be interpreted to only cover means for identifying polymorphisms (a polymorphism is a genetic variation) that are described in the specification. If the only means for identifying polymorphisms described in the specification rely on physically analyzing DNA molecules, the claim would appear to be so-limited and thus patent eligible.

Similarly, Claim 1 of 6,630,304 recites:

1. A method of diagnosing a susceptibility to osteoporosis in an individual, comprising detecting a polymorphism in a human BMP2 gene of SEQ ID NO: 1, wherein the presence of a "T" at nucleotide position 11980 is indicative of a susceptibility to osteoporosis, compared with an individual having an "A" at nucleotide position 11980.

This claim refers to detecting a genetic variation in a "gene," as opposed to a "sequence" (the language used by Myriad). If a court were to interpret the claim limitation "detecting a polymorphism in the gene" as requiring actual analysis of a DNA molecule (which could depend upon how the term "gene" is using the specification), the claim would appear to be patent eligible. However, if the claim is interpreted to encompass detecting a polymorphism by analyzing genetic sequence data, it would appear to be patent ineligible.

This is part of my criticism with jurists and lawyers untrained in metaphysics or logic. There is no sense in which the string representing the nucleotide sequence is "abstract," so to differentiate between them is to speak utter, illogical nonsense. Only the "idea" of the string is abstract, but whether you are using the actual, physical, polymer chain, or a symbolic representation of the chain, you are using physical entities, each of which expresses the same information in differing media. You are perpetuating a distinction with no difference in this entire line of reasoning, Chris.

This stuff just goes on and on. Patents have one sole purpose to protect the owners of the patents period. The users of products or services under patent are forced by law to pay unlawfull prices for their patented services and products. This decreasees demand for those products and services.

About Me

I am a law professor at the University of Missouri-Kansas City School of Law. My primary research interests lie at the intersection of biotechnology and intellectual property. This blog provides analysis and commentary on recent developments relevant to this area of the law.